eBooks

What is a low carb diet, really? When can a low carb diet be beneficial? Should everyone follow a low carb diet? Or, can a low carb diet ruin your health? After reading this eBook, you’ll be able to understand the many factors that play into how a person handles a low carbohydrate diet, and whether or not their health will improve on such a plan.

Is sugar “toxic” in any amount—even in natural sweeteners? Are artificial sweeteners safe? What about stevia and xylitol? Cut through the confusion and hype and find out which sweeteners are safe for you and your family.

Are common additives to food and supplements like soy lecithin, carrageenan, xanthum gum, and magnesium stearate harmful–or harmless? Read this eBook to find out which ingredients you should be concerned about, and which are safe.

An estimated 20 million Americans have thyroid disorders, but more than half don’t know it. Find out why thyroid problems are so often mis-diagnosed, what really causes them, and how to heal them naturally.

Research suggests that healing your gut may be the single most important thing you can do to improve your health. In this eBook, you’ll learn how to optimize your gut health—and by extension, your overall health—with simple diet and lifestyle changes.

What do memory loss, depression, anxiety, fatigue, nerve pain, and infertility have in common? They can all be caused by B12 deficiency. Find out why B12 deficiency is more common than most doctors think, how to know if you’re deficient, and what to do about it.

Does eating cholesterol and saturated fat really cause heart disease? Are statin drugs as effective as we’re told? Find out what the latest research says in this eBook, and learn how to prevent and treat heart disease naturally.

The Paleo diet has the potential to dramatically improve your health—but the transition doesn’t always go smoothly. In this eBook, you’ll learn the three biggest obstacles to Paleo success, and how to overcome them.

RHR: The Latest Discoveries in Evolutionary Biology, Genetics, and Epigenetics

I’ve always been fascinated by genetics and epigenetics, and what the study of those topics can tell us about human health and nutrition. We touched on this area a few shows back in my interview with Mat LaLonde, but I decided to devote an entire episode to it. I hope you enjoy listening to it as much as I enjoyed putting it together!

In this episode, we cover:

7:32 Debunking conventional wisdom about genetics11:42 Has evolution actually accelerated in the last 10,000 years?23:33 The role of environment in epigenetics and genetic mutations36:16 The pros and cons of evolution’s “light skin mutation”

Links We Discuss:

Full Text Transcript:

Steve Wright: Hi everyone, and welcome to another episode of the Revolution Health Radio Show. I’m Steve Wright from SCDlifestyle.com, and with me is Chris Kresser, health detective and creator of ChrisKresser.com. Chris, what’s going on?

Chris Kresser: I’m tired, Steve. Sylvie is getting a molar, and any of you who are parents out there, I’m sure, know what that’s like, and I’m pretty thin in the sleep department these days.

Steve Wright: Ah, she’s growing up fast.

Chris Kresser: Yeah, she’s getting teeth just, like, back to back to back. She’s gotten eight teeth in the past couple of months.

Steve Wright: Wow.

Chris Kresser: I don’t know if it’s all that bone broth we’re eating, cod liver oil, or what, but it’s been brutal on our sleep pattern, so if I nod off, just reach through the microphone and slap me around a little bit.

Steve Wright: Yeah, yeah, for sure.

Chris Kresser: How are you doing?

Steve Wright: I’m doing really well. We’ve got a little bit of a heat wave in the Midwest here, but luckily Michigan’s spared the worst of it. Got a big softball tournament this weekend I’m getting prepared for, and hopefully that’ll be a good time.

Chris Kresser: Good times, that’s right.

Steve Wright: OK. Well, before we get started, why don’t you take a little nap, and I’m gonna tell our listeners about —

Chris Kresser: Some coffee.

Steve Wright: OK, yeah. Coffee or tea. I got my tea next to me.

Chris Kresser: All right.

Steve Wright: All right, cool. So if you’re a listener and you’re new to the paleo diet or maybe you’re just interested in optimizing your health, you’re gonna want to check out what over 10,000 other people have signed up for. What’s this called? It’s called Beyond Paleo, and what it is is a free 13-part email series that Chris has put together over the past few years. It’s on all of his best tips and tricks on topics that are very relevant for you, including burning fat, boosting energy, and preventing and reversing disease without drugs. To sign up, go over to ChrisKresser.com and look for the big red box.

Chris, you got your coffee?

Chris Kresser: I’m good. I’m here. I’m awake.

Steve Wright: All right! Well, we’ve got a ton of show topics to cover today, so we don’t you kick us off?

Chris Kresser: OK, great. Yeah. So I actually want to start by just talking a little bit about my show with Mat Lalonde because judging from some of the comments on the show post and on Facebook, I think there may have been some misunderstanding and confusion, understandably, about what our intentions were. One listener, for example, left a comment saying something to the effect of “So are you guys saying that the paleo/primal diet is worthless?” And I just want to be really clear that that’s not what we meant to say at all, and I wish I would’ve been more clear about that in the show itself. The point of the show was really to examine which parts of the paleo diet can be supported by current scientific evidence. Modern scientific evidence, though, is only one way of obtaining information or making decisions. We have to always remember that. I’ve talked about this before, but lack of proof is not proof against, so in other words, just because we don’t have modern scientific evidence for something, that doesn’t mean it’s not true. Fifty years ago we didn’t have sufficient evidence that smoking caused lung cancer, but that didn’t mean that smoking didn’t cause lung cancer then, as we know that it does now. So it’s possible that in 10 or 20 years we’ll discover ways that grains and legumes affect human health that we’re not aware of yet.

And it’s also true that as Mat and I, I think, both pointed out in the show that just because some people may have some shallow genetic adaptations that enable them to better tolerate grains and legumes than others, that doesn’t mean that grains or legumes are optimal sources of nutrients or calories when compared to the foods that we’re more adapted to eat, like meat, starch, tubers, and fruit. And it also doesn’t take away from personal experience. So for example, I don’t eat grains other than white rice because I feel worse when I eat them, no matter how they’re prepared. So even if I soak them extensively in an acidic medium or, you know, with whey or kefir or yogurt or lemon juice, and I go through all the steps that you need to go through to make them more digestible, I still don’t feel great when I eat grains, so that’s really all the proof that I need, and I imagine it’s all the proof that most of you need too. If you try a paleo type of diet, you feel much better. Then maybe you experiment with reintroducing some grains, and you feel worse. I mean, that’s really the end of the story, from a practical perspective.

Now, I also wanted to make it clear that I’m nothing but grateful for the contributions of the paleo pioneers like Loren Cordain and Dr. Staffan Lindeberg. I’ve read all of their papers and books, and I have a deep appreciation for the work they’ve done really to introduce the paleo diet to the world and to their continuing efforts to validate it in the eyes of modern science. Now, I may disagree with them on certain small points. Like, I think white potatoes are well tolerated by most people unless they have an autoimmune issue, and I probably recommend consuming a little bit more saturated fat than they might, and I think dairy is beneficial when well tolerated, but these are small points, really, and they’re certainly, in my mind, not worth arguing about, and it’s really clear that we agree on far more than we disagree on. We’re talking about the same basic diet, just with some minor variations. And the fact is I wouldn’t be standing here talking to you if it weren’t for their prior work in this field. We’re all standing on the shoulders of others in this work, and I just have a lot of appreciation for the contribution that they’ve made, and I just want everybody to know that.

So yeah, I hope that clears anything up, any confusion up from that show. I obviously advocate a paleo type of diet. I wish I had a better name for what I advocate because everyone, I think, knows who has followed me for a while that what I advocate is not strictly paleo, but it’s based on what we could call a paleo template and with lots of room for individual modifications. But really what I’m talking about is pretty close to a paleo diet because that’s what I’ve found to be most effective in my own experience personally and as a clinician working with patients. So I hope that clears things up, and you know, if anyone has any questions about that, just let us know on Facebook or through the podcast submission link.

Debunking conventional wisdom about genetics

OK, so today I thought it would be interesting to talk a little bit more about genetics. We discussed genetics, I’ve touched on genetics in several different programs, and definitely Mat Lalonde and I talked about genetics when we had him on the show, but it’s a personal fascination of mine, and I think there’s been a lot of interesting new discoveries in the past couple of decades, and I think it would be fun to talk about them, especially in the context of the show that I did with Mat and the epigenetic changes that have happened recently that may have made us more adapted to some aspects of the modern lifestyle. And I think just having a better understanding of genetics is a helpful tool in understanding the larger questions that we talk about in terms of the influence of evolutionary biology on what’s optimal from a diet and lifestyle perspective.

So as we’ve discussed before, the conventional wisdom is that our genes haven’t changed much since the so-called Great Leap Forward 40,000 to 50,000 years ago in Europe, and this period of time marked the advent of cultural evolution and the end of significant biological evolution of humans. At least that’s the conventional theory. And this theory holds that when humans developed culture like tools or art or clothing, that basically freed us from pressures of natural selection. So in other words, we made clothes to keep us warm instead of growing fur, and we built better weapons to become more efficient predators rather than becoming stronger. But this idea that evolution stopped 40,000 to 50,000 years ago is dependent on the idea that our environment has been static since then. If a population experiences a stable environment for a long period, they eventually become genetically matched, but modern humans have, in fact, experienced huge changes in the past 50,000 years. We left Africa and settled on all the continents around the world except Antarctica. We encountered and eventually displaced archaic humans like Neanderthal and probably picked up some of their genes in the process. We’ve experienced a very rapid cultural explosion with new technology and social forms. And this geographical expansion and cultural innovation has really changed the selective pressure that humans experience.

So despite the common impression that evolutionary change is inherently slow, a lot of recent evidence suggests that natural selection can happen quite quickly, and this is just as true in humans as it is in domesticated animals and in plants. A really good example that most people will be familiar with is dogs. Dogs were domesticated from wolves about 15,000 years ago, and they now come in more varied shapes and sizes than just about any other mammal… well, definitely than any other mammal. Their behavior has changed a lot, too. Dogs are really good at reading human voices and gestures, for example, where wolves are not. Wolves pair bond with females and help raise their young, but dogs don’t. And we see kind of similar changes over a rapid period of time in domesticated plants. So, corn or maize is derived from a wild grass named teosinte, whose buds are about the size of a quarter, and this evolution from teosinte to the corn that we know of now that’s, you know, 6 or 7 feet high happened in just 7000 years, so that’s an extremely rapid pace of genetic change.

Has evolution actually accelerated in the last 10,000 years?

Harpending and Cochran are two evolutionary biologists or anthropologists, and they’ve written a book called The 10,000 Year Explosion: How Civilization Accelerated Human Evolution, which I think I’ve mentioned before. If you’re interested in this stuff, you definitely want to check that out. They and a lot of other evolutionary biologists and anthropologists now believe that human evolution has actually accelerated in the last 10,000 years. So it hasn’t slowed down or stopped, it’s actually gotten faster. In fact, they argue that the pace of evolution is happening about a hundred times faster than its long-term average over the last 6 million years and that humans have actually changed significantly physically and mentally over recorded history.

They do point out that most of these mutations are what they call shallow, which means they’re one mutation deep rather than a complex mutation, which involves several different genetic mutations. But they can still have a profound effect, and one of the best known examples, which we’ve discussed before, is lactase persistence. So 10,000 years ago, no humans could digest lactose after childhood. Mother’s milk was the only lactose-containing food available to our ancestors, and there wasn’t any point then in older children being able to digest it. And some anthropologists believe that shutting down the production of lactase may have served a social purpose in that it decreased destructive sibling rivalry. But after domestication of cattle during the Neolithic period, milk become widely available, and a mutation that continued production of lactase into adulthood originated about 8000 years ago and then has spread widely among certain populations, especially in Northern Europe. Lactase persistence, for example, has reached 95% penetrance in Denmark and Sweden, which means 95% of people in Denmark and Sweden have maintained the ability to digest lactose into adulthood. So this argument that you frequently hear that we’re the only mammal that drinks dairy of another animal and we don’t produce lactase so we shouldn’t drink it is actually false. It’s true that some cultures and some populations have really low rates of lactase persistence, for example, in Asia, but in other cultures, like in Northern Europe and in parts of Africa, like the Tutsi tribe in East Africa, they have quite high levels of lactase persistence.

And keep in mind that this all happened within a blink of an eye in evolutionary terms, less than 8000 years, and you often hear an argument that that’s not enough time for significant genetic changes to occur and that’s why we can’t be adapted to eat a neolithic food like dairy, but we have hard evidence of this kind of change. In 2007, researchers looked at DNA from skeletons of people who died between 7000 and 8000 years ago in Central and Northern Europe, where the frequency of lactase persistence is now about 80%, and none of the ancient European skeletons that they discovered had the allele for lactase persistence. But then another study of skeletons from the same area dating from the Bronze Age, which was about 3000 years ago, found that about 25% had the allele for lactase persistence. And then now, as I mentioned, in that same area lactase persistence is 80%. So that’s a really, really fast change over only about 7000 years.

There are other examples of really rapid genetic change, and one of them is the evolution of light skin in response to humans moving northward as well as new versions of genes involved in insulin regulation that probably resulted from exposure to higher-carbohydrate diets in the Neolithic period. So let’s take a little closer look at each of those. Most of you know by now that vitamin D is produced by UV light from the sun acting on our skin, and of course, less is produced further from the equator where UV flux is lower. Now, since there is some vitamin D in fresh meat, hunter-gatherers in Europe may not have suffered from vitamin D deficiency. They could probably get by even with their darker skin. But as people moved north and adopted agriculture, which meant that they ate less meat, vitamin D deficiency would have developed, decreasing resistance to infection, causing rickets, and even increasing the risk of cancer. This is probably why natural selection favored mutations causing light skin, which allow for adequate vitamin D production in areas of the world where there’s not as much UV radiation.

The other thing that happened when we moved north and transitioned to agriculture is we adopted a higher-carb diet, and this seems to have caused problems like tooth decay and diabetes that were rare among our hunter-gatherer ancestors. So some humans developed protective changes in the form of new versions of genes involved in insulin regulation. For example, researchers in Iceland have identified new variants of a gene regulating blood sugar that protects against diabetes, and those variants, interestingly enough, have different ages in the three populations studied: Europeans, Asians, and Sub-Saharan Africans. And in each of those populations, the protective variant is as old as agriculture is in that population. So that’s pretty strong evidence suggesting that those adaptations occurred directly in response to the adoption of agriculture.

Now, all of this said, given the long human generation time and the fact that agriculture represents less than 1% of the evolutionary history of the genus Homo, it’s unlikely that we’ve evolved any complex adaptations to an agricultural or industrial way of life, and this is what Mat and I pointed out and we talked about in that show. A complex adaptation is a characteristic that contributes to reproductive fitness involving coordinated actions of several different genes. So humans evolving wings or a third eye or some other complex adaptive behavior during that period could not have occurred. So this really suggests that although we have some shallow adaptations to our current environment and diet, it’s far from complete. And this is what Mat meant when he said — I’m gonna paraphrase this because he has a very specific way of saying it, but he said there’s been insufficient selective pressure for humans to completely adapt to our neolithic foods, so we may have some simple single-gene mutations that make some of us more adapted to modern foods than others, but again, that doesn’t mean that modern foods are an optimal source of nutrients and calories or that we wouldn’t be better off, even people who have those mutations wouldn’t be better off sticking to the foods that they’ve been adapted to eating for thousands of generations.

All right. I’ve been rambling on for a long time there, Steve. Any questions, comments on what we’ve talked about so far?

Steve Wright: Yeah. That was just really powerful, listening to you talk about the fact that… I think the most powerful thing for me was the fact that you’re saying that even if I was someone with a shallow mutation to a grain, the fact that it’s gonna be very shallow, one step, is likely to mean that I can tolerate it but it’s not gonna produce or really add to myself if I’m choosing to live a healthy lifestyle.

Chris Kresser: Yeah. I mean, there’s a spectrum. We tend to see things in black and white, but the reality is usually more gray. So if we look at foods on a spectrum of optimal on one end and toxic on another, most of the foods that we’re talking about fall somewhere in that spectrum. Even the “optimal” foods can sometimes have, you know, some less-than-desirable properties. So for example, leafy green vegetables like spinach. Spinach is high in oxalic acid, and that can cause problems for some people that are susceptible. We talked about that on the last Q&A episode. Spinach is also high in phytic acid, which can impair the absorption of nutrients from the food that it’s found in. But of course, spinach is an optimal food from a lot of other perspectives. So I think the goal is to be as close to that optimal end of the spectrum as possible, and so grains, especially when they’re not properly prepared, I think, are pretty… Even if you can eat them without any obvious negative effects like gut problems or skin issues or sinus problems or whatever, they’re not optimal as a source of nutrients because of all of the protective mechanisms that cereal grasses and seeds engage in to protect themselves from predators like us eating them. And this is, of course, what we talked about on the show with Mat, and there are a lot of traditional cultures that recognized that that developed ways of preparing cereal grasses and seeds and grains to break down those antinutrients and make them more digestible and absorbable. But still, when you compare the micronutrient content and protein content of those grains to something like meat or eggs or starchy tubers, meat and starchy tubers and fruit are gonna come out ahead almost every time. And it’s especially true if you add in organ means. There’s really no comparison. For me, you know, I think it’s a good idea to be as close to that optimal end of the spectrum as possible, and even if someone has, like you said, some of those adaptations that might make them more able to tolerate some modern foods, that doesn’t mean that those foods are optimal.

Steve Wright: Yeah, it’s just amazing to really think about the changes and… I mean, because I’m also thinking about something that you didn’t touch on, which is the epigenetics as well, and to think about the fact that the genes made a shallow adaptation over several thousand years and then the fact that epigenetics can happen much faster just… it’s really blowing my mind right now, but it’s really cool.

The role of environment in epigenetics and genetic mutations

Chris Kresser: Glad you brought that up, because it’s the perfect segue into our discussion about epigenetics, which is the next little phase here.

Steve Wright: Yeah, so are you gonna answer the question can we be epigenetically adapted to some of our neolithic foods? Is that possible?

Chris Kresser: I think there are probably some epigenetic adaptations that would make some of us more adapted. That’s certainly possible. But I don’t think that those adaptations, again, are going to change the nutrient density of foods. I mean, unless those adaptations are happening in the foods themselves, which… that hasn’t happened to the extent where grains are all of a sudden more nutrient dense and there are more bioavailable nutrients in grains than there are in meat and organ meats and other animal products and starchy tubers and fruit.

Steve Wright: I think I might have also answered my own question there. You don’t have, like, an epigenetic anti-gluten potion that just comes out, so… we don’t have that change yet.

Chris Kresser: So far, we haven’t seen that. So let’s talk a little bit about epigenetics. It used to be thought that our genetic code was written in stone and what we get is what we get and that’s it, but now we know that changes in gene expression without changes in the underlying DNA can be incredibly significant and that these changes are triggered by environmental factors, so not from heritable genetic factors, but environmental factors that can even be passed from one generation to the next. There’s a famous study that Mat and I talked about in 2003 where they took fat yellow mice that always gave birth to other fat yellow mice, and researchers gave them a bunch of supplements to improve methylation, which is involved in DNA silencing, and those fat yellow mice gave birth to skinny brown mice. And the interesting thing about it was that the genes were exactly the same in the skinny brown mice. They were right in the same positions where they were supposed to be, but somehow the methylation supplements turned the gene that made those mice fat and yellow off so that the baby mice still had the gene but it wasn’t expressed. And that process of genetic suppression is called DNA methylation, and methylation happens when a compound called a methyl group binds to a gene and changes the way it expresses itself. And there are a lot of examples of this kind of phenomenon in both animals and humans. A few of them that some of you might have heard of are that depending on the time of year that they’re born, baby voles are either born with a thick coat or a thin coat, so the gene for the thick coat is always there, but it’s just turned on or off, depending on the level of light that the mother senses in the environment when she’s pregnant. Another example is that the mother of the fresh water flea Daphnia will produce offspring with a larger helmet and spines if it’s going to give birth in an environment that’s crowded with predators. So they actually are born more or less heavily armed depending on what kind of environment they are born into.

And this happens even in humans. David Barker in the UK found 20 years ago that babies that were born at low birth weight that were undernourished during pregnancy are more likely to be obese and experience metabolic problems later in life. So what’s happening here is that in Paleolithic times, if a baby was born into a time of scarcity and famine, their metabolism would be much more efficient at extracting energy from food. This is the thrifty metabolism hypothesis. And that would help it survive in that kind of environment. But unfortunately, today in an environment with endless availability of calorically dense foods, this thrifty phenotype where the baby is born with this propensity to extract very efficiently calories from food will end up causing obesity and other metabolic problems. So these are a few examples of how our environment can trigger epigenetic changes that then lead to very real changes in our physiology and biology later on in life and even throughout the rest of our lives. These aren’t just changes that happen in early infancy. They are changes that affect us for the rest of our lives.

There are some other genetic mutations that can occur rapidly that have a dual effect. This is another interesting way of looking at it because we tend to think of mutations as things that are beneficial, and they are, but what’s beneficial from an evolutionary perspective might not always be beneficial from a longevity perspective, and that’s because evolution is mostly concerned about our reproductive fitness. So once we’ve reproduced, if a mutation can actually improve our ability to reproduce and the likelihood that we’ll reproduce successfully but at the same time it decreases our lifespan after reproductive age, evolution doesn’t really care about that. That’s still a win from evolution’s perspective.

An example of this is hemochromatosis, which we’ve discussed a few times, and actually iron overload is gonna be the subject of my talk at the Ancestral Health Symposium in August this year. Hemochromatosis is a genetic mutation that causes iron overload, and recent research suggests that it originated with a single Viking or Celtic ancestor as recently as 2000 years ago, so that’s very recent, and that it spread through Northern Europe as Vikings colonized the European coastline. Now, there are a lot of different theories for how this mechanism came about. Some people think it may have evolved as a way of minimizing iron deficiency in poorly nourished populations that were living in harsh environments, but if this were the case, you’d expect to find hemochromatosis in all populations living in iron deficient environments, and you don’t. Other researchers have speculated that women you had hemochromatosis might have benefitted by addition iron because it prevented anemia from menstruation, but again, you’d have to explain why it’s not a more prevalent mutation around the world because women menstruate everywhere. Another theory suggests that Viking men may have offset the negative effects of hemochromatosis because their warrior-like culture resulted in frequent blood loss. That’s possible too, but it’s always seemed like a bit of a stretch to me.

The most convincing theory I’ve come across is that hemochromatosis increased in frequency due to something called the founder effect. So when small populations establish colonies in unpopulated or secluded areas, you get significant inbreeding for many generations, and this inbreeding pretty much guarantees that any mutations that aren’t fatal at an early age will be maintained in large portions of the population. So how did this work in the case of hemochromatosis? Well, in the mid-1350s, the bubonic plague was spreading across Europe and killing millions of people, a significant percentage of the population, in fact. But people with hemochromatosis, as it turns out, are resistant to infection because even though their tissues are iron-loaded, their macrophages, which is the type of white blood cell that fights infections, have very little iron in them. And infectious organisms — all organisms, in fact — utilize iron. And bacteria and viruses and parasites and yeast thrive on iron, so because these macrophages that were fighting infections have very little iron in them, the infections couldn’t thrive in these people with hemochromatosis. So even though the hemochromatosis probably ended up killing them a few decades later from, you know, cirrhosis of the liver and other complications, heart disease, they were much more likely than people without hemochromatosis to survive the plague and then reproduce and pass that mutation on to their children. So the growing percentage of hemochromatosis carriers in that period may also explain why no subsequent plague after that initial one was as deadly. That’s pretty fascinating to me, is that a mutation that really shortens our life expectancy and can cause some really nasty problems in older age may have persisted simply because it conferred protection against a more immediate threat to our survival at a given point in time.

Steve Wright: Yeah, that’s pretty crazy. I did not know that history.

Chris Kresser: Yeah. It’s really fascinating.

Steve Wright: My mind is racing right now. So I just want to say this generalization, because I’m thinking some other people listening might be thinking like this too, and then I want to hear what your thought are on it. So, really general here: So our genes obviously are all slightly different but all basically the same, and the predominant genome right now or most of us are not carrying the shallow mutation to most neolithic foods, and so when we eat them, then we are using epigenetics, and those foods in the current environment that we’re in are gonna trigger our epigenetics to allow us to survive the best we can, but when we make those switches, you know, it’s a tradeoff. Is that where all of these lifestyle diseases that we’re talking about, heart disease and diabetes — Is that what we’re really talking about here?

Chris Kresser: Yeah. I mean, that’s one way of looking at it. A couple of things are, number one, we don’t really know what percentage of the population has single-nucleotide polymorphisms or the single-gene mutations that have made us more adaptable. I mean, we know of certain pockets. I mentioned some of those earlier. But we don’t really have a clear sense, and there’s not really any way to accurately test for that. And in terms of epigenetic changes, that depends too. So I mean, one way that this can work is if you look at methylation as an example, and somebody adapts a diet that’s mostly based on grains, a vegetarian or vegan diet that’s mostly grain-based, they’re gonna be deficient in B12, and B12 is a crucial part of that methylation cycle. And if they’re not methylating properly, then they may not be able to silence certain expression of certain genes, and that then leads to an epigenetic change that could have ill health consequences. That’s one example of how diet can directly affect epigenetic gene expression. But there are a lot of other examples too, and yes, that is probably how… I mean, that’s what happens when you give a bunch of human animals types of food that we’re not really adapted to eat. Then that’s gonna have consequences like these increases in modern disease that you mentioned.

Steve Wright: So fascinating. I know we don’t know all the answers, we’re not even close to figuring it out, but the fact that science is just, you know… It seems like every 10 years we’re making quantum leaps about understanding what’s happening. It’s pretty amazing.

The pros and cons of evolution’s “light skin mutation”

Chris Kresser: It is pretty exciting. So let’s take a closer look at the light skin mutation I mentioned earlier, because that’s fascinating too from this perspective of where you get kind of a push and pull or give and take in these genetic mutations where they’re beneficial in some ways and maybe not in others. Most people are aware that sunlight helps the body create vitamin D. When we’re exposed to UVB light, the body converts cholesterol actually into vitamin D, which is another reason why lower isn’t always better with cholesterol. And the further north we get from the equator, as I said, the less UV light there is, especially during the winter months.

And here’s an interesting side note, by the way: The next time you get your cholesterol checked, pay attention to what season it is because, because sunlight converts cholesterol to vitamin D, cholesterol levels tend to be higher in the winter months when there is less sunlight available to convert it. And I actually didn’t know that until fairly recently. So there’s a seasonal variation in cholesterol levels for that reason.

But what fewer people know is that sunlight not only aids in the creation of vitamin D, but it actually destroys the body’s reserves of folate, which is a crucial B vitamin involved in cell growth and, again, in methylation. Because of folate’s role in DNA replication, it’s especially important during pregnancy, and when a pregnant woman’s folate is low, she’ll have a significantly higher risk of serious birth defects like spina bifida and neural tube/neural crest/cranial defects. In the mid-1990s, an Argentinian pediatrician reported that three healthy women all gave birth to children with neural tube defects after repeatedly using indoor tanning beds during their pregnancies. This is one of studies that led to this understanding that sunlight destroys folate reserves.

So the skin is responsible for protecting the body stores of folate, and the skin is where the manufacturing of vitamin D takes place, so you might already know that the wide range of human skin color is related to the amount of sun a population has been exposed to over a long period of time. But darker skin is not just an adaptation to protecting against sunburn. It’s also an adaptation to protect against the destruction of folate by UV light. So the darker your skin, the less ultraviolet light you absorb, and skin color is determined by the amount and type of melanin, which is a pigment that absorbs light. So as some populations moved north where sunlight was less frequent and less strong, dark skin that was designed to block UV absorption no longer served us. Instead of protecting against the loss of folate as it did in the tropical climates with more sun, it was preventing the creation of vitamin D. So this evolutionary pressure led to selection for genes for lighter skin. And in fact, an article in the Journal of Science recently went as far as saying that Caucasians are actually black skin mutants who lost the ability to produce a significant amount of eumelanin, which is the black or brown pigment. So what’s amazing about this is that we carry sufficient genes within our gene pool that within a thousand years of a population’s migration from one climate to another, its descendants would have a skin color dark enough to protect folate or light enough to maximize vitamin D production. So if you took a bunch of Swedish people and you moved them down equatorial Africa, within a thousand years they’d all have very dark skin, or vice versa. So some of you might be thinking of one exception, the Inuit, who are dark-skinned people despite the very limited amount of sunlight they get where they live. But the reason they didn’t need to evolve lighter skin to ensure sufficient vitamin D production is that they eat it for every single meal. Seal meat and cod liver oil are extremely high in vitamin D, so they didn’t need to rely on the sun for vitamin D production.

And you might also be wondering how dark-skinned people produce enough vitamin D, and this actually involved another genetic adaptation, and dark-skinned people tend to be carriers of apolipoprotein E4. This is a single nucleotide polymorphism, or SNP, of the apolipoprotein E gene. And ApoE4 carriers have higher levels of LDL cholesterol than the more common ApoE3 and ApoE2 genotype. This means they have more cholesterol available for conversion of UV light to vitamin D, and carriers of ApoE4 can, in turn, compensate for limited ultraviolet light exposure. And sure enough, it’s not only people with darker skin that tend to be ApoE4 carriers, but that phenotype is also common in northern latitudes where exposure to UV light is low, like in Northern Europe. And this is yet another example of where a mutation that happened to prevent one thing from going wrong could have led to some undesirable consequences. So ApoE4 carriers have a higher risk of Alzheimer’s and dementia, and they have a higher risk of heart disease. And you know, the conventional view is that they have that higher risk because of higher levels of LDL, but actually the most recent research and our recent understanding of what causes both Alzheimer’s and heart disease suggests that the reason they have a higher risk is that ApoE4 carriers are more susceptible to oxidative damage and inflammation, and it’s the oxidation of the LDL particle that’s the common thread in both increased risk of heart disease and increased risk of Alzheimer’s and dementia. So this ApoE4 mutation that helps dark-skinned people produce vitamin D and also lighter-skinned people in northern latitudes produce enough vitamin D wouldn’t have been a problem in an environment where oxidative risk factors were low, like people weren’t smoking, they were getting plenty of exercise, their stress levels were managed, they weren’t eating a lot of omega-6 polyunsaturated fat that has the potential to oxidize. But in this modern world where the modern lifestyle is full of oxidative risk factors, then this ApoE4 mutation has a dark side. So I just find it fascinating. I mean, it’s like our genetic code is doing the best that it can to make us healthy and protect us from harm, but the lifestyle that we’re living keeps kind of throwing a monkey wrench in the plan.

Steve Wright: Yeah, that’s the innate body wisdom, it sounds like.

Chris Kresser: Um-hum, that we’ve kind of overridden in some ways with our just rapid cultural expansion, that those things happened so quickly and so unintentionally in a way. I mean, there isn’t a master plan there and all of a sudden we’ve got Super Big Gulps and Cheetos and all kinds of packaged, processed, and refined foods. It’s just because we can without really realizing the effect that that’s gonna have on our biology.

Steve Wright: Yeah, and the other thing, I’m just in a really grateful headspace right now with this idea that we’re now gaining enough scientific knowledge to understand is currently happening in real time almost. And if you’re like you or me and you choose to honor your other genes, the ones that haven’t mutated yet, you’re sort of, like, creating your own evolution. You know, you’re not allowing… The rest of society is still running towards their Big Gulps, which is gonna continue to create changes, and there are whole pockets of us who are deciding to not do that, so that’s really interesting to think about.

Chris Kresser: Yeah. I mean, it is a really exciting time to be involved in this stuff because the pace of change is just so rapid, and I do think our understanding is growing by leaps and bounds. And at the same time, I’m also humbled by how much we don’t understand, and I really try to keep that in mind because, I mean, even just looking back at the few years that I’ve been involved in this, my views have shifted considerably on certain issues, and I hope that that continues to happen because… I don’t know. I mean, I’ve said this before, I think, but my experience is that the more I get into something and learn about something, the more I realize I don’t know about it. And that’s true for me with things like martial arts. Like, you know, when I first started and I was 17 years old and training in martial arts, after a little while I thought I knew a lot about it and I was pretty good.

Steve Wright: Hot stuff!

Chris Kresser: Yeah! I was hot stuff, you know, when I was 17. And 20 years later, I’m just like, wow, I feel like such a beginner, you know, and there’s so much I don’t understand and need to learn. I think when I first started getting into the nutrition and research world, it was a similar thing. I was like, oh, yeah, I’ve got this stuff figured out. And then the deeper you get into it, the more I realize, wow, this is endless. I could spend a lifetime and still have so many questions, you know, maybe more questions than when I started. So it’s a good thing to keep in mind, and it is humbling, but the good news is I think we know enough to be able to make really practical decisions about how to live and eat that can lead to better health. And at the end of the day, that’s really what matters. That’s what most people care about. And we’ve got plenty of good information to go on, as far as that goes.

Steve Wright: Yeah, I agree, and I couldn’t agree more with the humbling thing, except for it’s usually me being humbled as I listen to you speak, so thank you.

Chris Kresser: Ha-ha! So I think that’s a good place to stop. I know we had some questions, but I need to go take a nap.

Steve Wright: What?! Chris Kresser takes naps?!

Chris Kresser: No, not usually, but when I’ve slept about a grand total of maybe eight hours in the past four or five nights, I think a nap is starting to sound like a good idea.

Steve Wright: I think that’s a good thing for you.

Chris Kresser: Yeah. All right, well, we’ll see you all in a couple weeks. Thanks for listening, as always, and enjoy the 4th of July weekend.

Steve Wright: Yeah, thanks for listening, everyone. And if you enjoyed what you heard today, please head over to iTunes and leave us a review. It helps us to get better rankings and share the message with more people. And if you have any more questions for us, please head over to ChrisKresser.com and use the podcast submission link. So have a great 4th of July, and we’ll talk to you soon.

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Chris,
I’m very confused regarding a diet for myself. I’ve been following a Paleo diet and my cholesterol has been climbing. As I’m adopted, my MD suggested genetic testing and I carry APOE 3/4. He doesn’t think dietary changes will help but something has to benefit those of us in this category. I’m caucasian and the testing says I’m of Irish decent. If you have suggestions, I’d be so grateful! Bonnie

You mentioned at APOE4 variant earlier and I just wondered if you could make recommendations on diet changes for these individuals. I’ve read on other blogs that saturated fat is bad for them? Any help is greatly appreciated

I enjoyed this, tho I’d endorse Ricardo’s comment.
Re: lactase persistence; we all have genes for lactase at birth. We don’t LOSE genes as we age, surely? So lactase persistence is probably an epigenetic adaptation of some sort.

During the discussion of how skin tone adapts to sun exposure in about 1,000 years, it made me think of how rapid people have moved around the globe. Probably even 100 years ago it would have been relatively rare for people to move from one climate extreme to another. However in today’s world, there are many more people who end up living in their ‘non-native’ climate. It seems there would likely be other effects of that (different food sources, different beneficial bacteria, etc.) that might be showing up in our health today, or perhaps it will impact the health of the next generations.

ME TOO!!!! I think that all the time. Plus we don’t have normal sunlight exposure. I’m a whitey, of Irish and German and English descent. If I were outside all spring then by summer I would have enough of a tan to handle the full days, with some shade while hunting and gathering, at my ancestral latitude. But I live in CO, which is not only lower in latitude but also 1 mile in elevation, so not so much protection from the UV. If I were a native I wouldn’t worry about sunlight on a day to day basis here, but natives from CO are much darker than I. I try really hard to get a good amount of sun but not get burned, but it’s so hard to know when I’m burning or not! I just wish my body would tell me “hey you’re about to burn!”.

I echo Adrian’s comment. I was born with mild spina bifida (didn’t completely penetrate the nerve sack I’m told) so I always take folate. While I was pregnant with my son my mid wife sent me for extra testing to monitor things. I read your post on the proper kind of folate to take and I’m so happy that I am now taking the right kind.

Planning to start trying for another baby in about a month, so I’ve been trying to get some extra sun in up here in Canada, I figured the Vit D and other benefits would be good for a developing baby. Now I’m wondering if that might be dangerous for someone with a genetic history of neural tube defects.

Fascinating topics covered. I’m particularly interested in the discussion of sunlight exposure depleting levels of folate, and the potential flow on effect on birth defects.

In this case, do you have any recommendations for limiting sun exposure prior to / during pregnancy? If this is the case, is this limited to only the early stages of pregnancy where I believe sufficient folate is most critical in the 3rd/4th weeks of pregnancy for preventing spina bifida?

Dear Dr Kresser:
In the paleo literature we constantly talk about the Neolithic revolution that took place 10,000 years ago when we shifted to agriculture. In this show you mention how some genetical adaptations may have taken place in this short period of time (such as lactose tolerance and skin colour). Bear in mind, however, that for most of humanity outside Europe, this change took place a lot later. In “The Cambridge Encyclopedia of Hunters and Gatherers”, we read: ‘By AD 1500, on the eve of European expansion, hunter-gatherers still occupied almost one third of the world’s landmass, including all of Australia, the North Western half of North America, and the southern part of South America…’ (p. 389). Later on they write: ‘At the beginning of the industrial Revolution, the Western colonial powers had made claims over 55 per cent of the world’s land area but exercised effective control only over 33 per cent of the world; much of the uncontrolled territory … was still effectively controlled by hunting and gathering, or foraging peoples’ (p. 467).
So we can conclude two things: one, hunting gathering has been much more successful as an economic model than we give it credit for, and two, we tend to be a bit too ‘Euro-centric when we talk about these 10,000 years of agriculture.
Cheers!

Chris, another amazing podcast here. Your passion and knowledge are both inspiring and humbling. SO much interesting stuff, I read the transcript twice and will likely return again. Thank you so very much for doing what you do.